While lens crystallines have been extensively studied, very little is known about the cytoskeletal proteins of the lens. Spectrin and ankyrin, major protein components of the cytoskeletal architecture, have recently been identified in the human lens. The lens has been found to contain erythroid and non-erythroid spectrin mRNA transcripts in amounts exceeding that of any other studied human tissue. Lens cells and red blood cells share many similarities (absence of nuclei, limited metabolism, preponderance of anaerobic glycolysis, etc.). Spectrin and ankyrin have been extensively investigated in red cells, and great progress has been made in their characterization. We have recently identified unique, and in some instances, multiple transcripts of the erythroid-specific alpha and beta spectrins, as well as non-erythroid alpha subunits in human lens. Lens mRNA transcripts of these genes were present in abundant quantities, exceeding that found in other tissues. We plan to identify the structure and function of spectrins and ankyrin in the lens cytoarchitecture, utilizing recombinant DNA technology. Additionally, experiments will be performed for immunolocalization of various spectrin and ankyrin peptides at the cellular as well as subcellular levels. Many abnormalities of spectrin and ankyrin have been identified as causes of specific red cell morphologic abnormalities associated with congenital hemolytic anemias. The role of mutants of these proteins in lens pathology remains to be established. An ample supply of human lenses are available for this study. A significant population of patients with a variety of genetic spectrin and ankyrin abnormalities are also available and a detailed ophthalmological assessment of these patients will be performed in order to evaluate concomitant lens and other ocular pathology. Specific mutants will be characterized by recombinant DNA technology.